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Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study

Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study
Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study
Background The common isoforms of apolipoprotein E (apoE), E2, E3, and E4, are important determinants of plasma lipid concentrations, and the ?4 allele is associated with raised risk of coronary heart disease. We investigated whether the effect of smoking on coronary heart disease risk is affected by APOE genotype.
Methods We enrolled 3052 middle-aged men who were free of coronary heart disease for prospective cardiovascular surveillance in the second Northwick Park Heart Study (NPHSII). Smoking habit was ascertained at baseline and yearly by questionnaire. APOE genotype was identified by PCR and restriction enzyme digestion. Endpoints were fatal coronary heart disease, non-fatal myocardial infarction, and coronary artery surgery and silent myocardial infarction at follow-up.
Findings During 18 836 person years of surveillance, 96 men had an acute myocardial infarction, 26 needed coronary artery surgery, and 14 had silent myocardial infarctions. Compared with never-smokers, risk of coronary heart disease in ex-smokers was 1·34 (95% CI 0·86–2·08) and in smokers it was 1·94 (1·25–3·01). This risk was independent of other classic risk factors. In never-smokers, risk was closely similar in men with different genotypes. Risk in men homozygous for the ?3 allele was 1·74 (1·10–2·77) in exsmokers and 1·68 (1·01–2·83) in smokers, whereas in men carrying the ?4 allele risk was 0·84 (0·40–1·75) and 3·17 (1·82–5·50), respectively, with no significant differences in risk in the ?2 carriers. For the 3 group, the genotype effect on risk was no longer significant after adjustment for classic risk factors (including plasma lipids). However, even after adjustment, smokers who were carriers of the ?4 allele, showed significantly raised risk of coronary heart disease compared with the non-smoking group (2·79, 1·59–4·91, ·4-smoking interaction p=0·007).
Interpretation Smoking increases the risk of coronary heart disease in men of all genotypes but particularly in men carrying the ?4 allele.
0140-6736
115-119
Humphries, S.E.
ccc89458-fe7c-4cce-92a3-470dac1b33b6
Talmud, P.J.
6921755a-49e5-4a12-b4b7-051c19091974
Hawe, E.
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Bolla, M.
7071a3c6-b6d1-45eb-b486-bb0ab071bc51
Day, I.N.
e9cacaf7-f4c8-4ef0-82fa-b459ad683d50
Miller, G.J.
c0be8252-47b0-4482-a977-25ac06cf59df
Humphries, S.E.
ccc89458-fe7c-4cce-92a3-470dac1b33b6
Talmud, P.J.
6921755a-49e5-4a12-b4b7-051c19091974
Hawe, E.
04b00658-cb75-42fc-9213-9c3ba8372105
Bolla, M.
7071a3c6-b6d1-45eb-b486-bb0ab071bc51
Day, I.N.
e9cacaf7-f4c8-4ef0-82fa-b459ad683d50
Miller, G.J.
c0be8252-47b0-4482-a977-25ac06cf59df

Humphries, S.E., Talmud, P.J., Hawe, E., Bolla, M., Day, I.N. and Miller, G.J. (2001) Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study. The Lancet, 358 (9276), 115-119. (doi:10.1016/S0140-6736(01)05330-2).

Record type: Article

Abstract

Background The common isoforms of apolipoprotein E (apoE), E2, E3, and E4, are important determinants of plasma lipid concentrations, and the ?4 allele is associated with raised risk of coronary heart disease. We investigated whether the effect of smoking on coronary heart disease risk is affected by APOE genotype.
Methods We enrolled 3052 middle-aged men who were free of coronary heart disease for prospective cardiovascular surveillance in the second Northwick Park Heart Study (NPHSII). Smoking habit was ascertained at baseline and yearly by questionnaire. APOE genotype was identified by PCR and restriction enzyme digestion. Endpoints were fatal coronary heart disease, non-fatal myocardial infarction, and coronary artery surgery and silent myocardial infarction at follow-up.
Findings During 18 836 person years of surveillance, 96 men had an acute myocardial infarction, 26 needed coronary artery surgery, and 14 had silent myocardial infarctions. Compared with never-smokers, risk of coronary heart disease in ex-smokers was 1·34 (95% CI 0·86–2·08) and in smokers it was 1·94 (1·25–3·01). This risk was independent of other classic risk factors. In never-smokers, risk was closely similar in men with different genotypes. Risk in men homozygous for the ?3 allele was 1·74 (1·10–2·77) in exsmokers and 1·68 (1·01–2·83) in smokers, whereas in men carrying the ?4 allele risk was 0·84 (0·40–1·75) and 3·17 (1·82–5·50), respectively, with no significant differences in risk in the ?2 carriers. For the 3 group, the genotype effect on risk was no longer significant after adjustment for classic risk factors (including plasma lipids). However, even after adjustment, smokers who were carriers of the ?4 allele, showed significantly raised risk of coronary heart disease compared with the non-smoking group (2·79, 1·59–4·91, ·4-smoking interaction p=0·007).
Interpretation Smoking increases the risk of coronary heart disease in men of all genotypes but particularly in men carrying the ?4 allele.

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Published date: 2001
Organisations: Human Genetics

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Local EPrints ID: 24774
URI: http://eprints.soton.ac.uk/id/eprint/24774
ISSN: 0140-6736
PURE UUID: 1ccef17a-3af6-4db8-ad5b-2956eec10a0a

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Date deposited: 04 Apr 2006
Last modified: 15 Mar 2024 06:58

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Contributors

Author: S.E. Humphries
Author: P.J. Talmud
Author: E. Hawe
Author: M. Bolla
Author: I.N. Day
Author: G.J. Miller

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